Development of lipogenesis and insulin sensitivity in tissues of the ob/ob mouse.
Lipogenesis and insulin sensitivity are evaluated in adipose tissue, liver, and diaphragm of ob/ob and non-ob/ob mice. In ob/ob mice, hepatic fatty acid synthesis from [U-14C]glucose is elevated by 4 wk of age, and adipose tissue fatty acid synthesis increases at approximately 7 wk. Hepatic activities in ob/ob mice of glucose-6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), malate dehydrogenase (EC 1.1.1.40), and alpha-glycerophosphate dehydrogenase (EC 1.1.1.8) are dramatically increased by 7 wk of age. Diminished insulin-stimulated glycogen synthesis is first noted in the diaphragm of ob/ob mice at 7 wk of age. Insulin-stimulated glycogen synthesis in adipose tissue of ob/ob mice is impaired at 3 wk. At 7 wk, insulin-stimulated fatty acid synthesis in adipose tissue of ob/ob mice is markedly increased. Adipose tissue glyceride-glycerol synthesis continues to increase throughout development, whereas fatty acid synthesis decreases after 7 wk. The data suggest that alterations in lipid synthesis occur very early in the development of ob/ob mouse, prior to expression to overt obesity, at which time a major contribution to lipogenesis is made by the liver. The altered de novo lipogenesis does not precede the reported diminution in energy metabolism.
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D003964:Diaphragm / Q000378:metabolism*; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005990:Glycerol; D005991:Glycerol Kinase / Q000378:metabolism; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D006003:Glycogen; D007328:Insulin / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism*; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism
D005227:Fatty Acids; D007328:Insulin; D006003:Glycogen; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005991:Glycerol Kinase; D005990:Glycerol